Healing of osteoporotic bone defects by baculovirus-engineered bone marrow-derived MSCs expressing MicroRNA sponges

Li, Kuei-Chang; Chang, Yu‐Han; Yeh, Chia-Lin; Hu, Yu‐Chen

doi:10.1016/j.biomaterials.2015.09.046

Cited by 93 publications

(85 citation statements)

References 57 publications

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“…Osteoporosis is carried out by excessive bone destruction by osteoclasts coupled with insufficient bone formation by osteoblasts, resulting in reduction of bone mass and low trauma fractures [1,2]. MicroRNAs (miRNAs) are evolutionarily conserved, small (~22 nucleotides), singlestranded non-coding RNAs that silence the expression of specific gene by base-pairing to the 3'-untranslated regions of target mRNAs on post-transcriptional level [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Tang¹,

Yin²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure. Methods: First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124. Results: BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis. Conclusion: Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.

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Section: Introductionmentioning

confidence: 99%

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Tang¹,

Yin²,

Liu³

et al. 2017

Cell Physiol Biochem

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“…[107] Many distinct scaffold types have been tuned to serve the purpose of miRNA delivery, including several hydrogels, [58,92,106,[108][109][110][111][112][113][114] electrospun fibers, [63,[115][116][117][118] and more prolifically porous or spongy scaffolds. [46,47,50,54,55,96,112,[119][120][121][122][123][124][125][126][127][128][129][130] Before reviewing the details of their applications, summarized in Table 2 and described further in the next section, we will discuss the key characteristics making these materials amenable to miRNA delivery. First very general qualities must be fulfilled: biocompatibility, bioresorbability and ease of fabrication.…”

Section: Scaffolds For Microrna Deliverymentioning

confidence: 99%

“…Osteoporotic bone defects have also been healed by BV-engineered OVX-BM-MSCs expressing miRNA sponges carrying miR-214 either alone or in combination with BMP2. [130] This assessment was carried out by implanting gelatin Spongostan scaffolds preseeded with transduced OVX-BM-MSCs. Coexpression of BMP2 plasmid and miR-214 sponges in OVX-BM-MSCs enhanced synergistic healing.…”

Section: Osteogenesis and Bone Repairmentioning

confidence: 99%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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“…Therefore, mmu-miR-34a-5p might be a conceivable therapeutic target for GCOP (Kang et al, 2016a). Li et al reported that mmu-miR-140-3p and mmu-miR-214-3p impeded sponges via constructed Cre/loxP-based hybrid baculovirus vectors, demonstrating improved bone formation and mitigated excessive bone resorption in an osteoporotic bone defect rat model, thus paving a new avenue to the treatment of osteoporotic bone defects through combination of osteogenic factors and functional miRNAs (Li et al, 2016c). In addition, Krzeszinski and colleagues found that mmu-miR-34a-5p knockout and heterozygous mice exhibited elevated bone resorption and reduced bone mass by targeting transforming growth factor-b-induced factor 2 (Tgif2), indicating that miR-34a-5p was a critical osteoclast suppressor and a potential therapeutic strategy to combat osteoporosis, and could exert both anti-catabolic and anabolic effects compared to current drugs that are solely anticatabolic (Krzeszinski et al, 2014).…”

Section: Osteoporosismentioning

confidence: 99%

Small non-coding RNAs-based bone regulation and targeting therapeutic strategies

Yang

Fang

2017

Molecular and Cellular Endocrinology

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Small non-coding RNAs, which are 20-25 nucleotide ribonucleic acids, have emerged as an important transformation in the biological evolution over almost three decades. microRNAs (miRNAs) and short interfering RNAs (siRNAs) are two significant categories of the small RNAs that exert important effects on bone endocrinology and skeletology. Therefore, clarifying the expression and function of these important molecules in bone endocrine physiology and pathology is of great significance for improving their potential therapeutic value for metabolism-associated bone diseases. In the present review, we highlight the recent advances made in understanding the function and molecular mechanism of these small non-coding RNAs in bone metabolism, especially their potentially therapeutic values in bone-related diseases.

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Healing of osteoporotic bone defects by baculovirus-engineered bone marrow-derived MSCs expressing MicroRNA sponges

Cited by 93 publications

References 57 publications

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Small non-coding RNAs-based bone regulation and targeting therapeutic strategies

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